1. TECHNOLOGY UPDATE TIVUS (Cardiosonic)
Klaus Hertting
Park-Hospital
Leipzig, Germany

2. I have no real or apparent conflicts of interest to report.
Klaus Hertting, MD
I have no real or apparent conflicts of interest to report.

3. Cardiosonic TIVUS™ System and Setup for Renal Denervation
6 Fr TIVUSTM
Console – illustration
5 F shaft; 6F tip _ contrast injection during treatment possible 3

4. Non-Focused High Intensity Ultrasonic Catheter
Core Technology:
Non-Focused High Intensity Ultrasonic Catheter
Non-Focused Ultrasonic Ray
Cooling effect by the blood flow
T [C0]
Depth into artery [mm]
Thermal Effect Threshold

5. Renal Denervation Using TIVUSTM: Localized Targeted Nerve Damage
Renal Denervation Symplicity® vs. TIVUSTM:
Swine Study, TTC Stain and H&E Histology 10/01/2012
(Leipzig, Germany)
Renal Artery Cross-Section
Large nerve fibers bundles with fat cover
Nerve fibers
Aorta
Lumen
Adventitia
Media
Intima/
Endothelium

6. Pre Clinical Results
Ultrasonic Transducer
High intensity ultrasonic beam
TIVUS™ Catheter
Safety: no significant kidney function alteration and no significant angiography luminal narrowing
Remote effect: No contact with the luminal wall, endothelial sparing
Localized effect: Within the ultrasonic ray
Thermal Modulation: Controlled effect size by parameters
Effective: NE concentration lower by up to 93% compared to independent untreated animals.

7. TIVUS™ Treatment Protocol
12 o'clock
6 o'clock
3 o'clock
9 o'clock
1-3 treatment sites along the artery. Up to 4 circumferential treatment points per site, 90°rotation.
Clear angiographic imaging of treatment head circumferential positioning.
Ultrasonic position feedback. Minimal need for contrast injection
Next Generation TIVUSTM:
single-operation
simultaneous circumferential treatment

8. The TIVUS™ Technology Advantages for Renal Denervation
Remote, localized, and controlled thermal modulation of vessel wall tissue components
Prevents disruption of the endothelium, elastic lamina, and other surrounding tissues
Energy delivery without physical contact with the vessel intima
Non-occlusive catheter with no collateral tissue damages
Real-time ultrasonic positioning feedback for safety
Simply fluoroscopically guided treatment
Short excitation: seconds per treatment point

9. TIVUS™ I Study
The TIVUS™ I First In Man Study; Prospective, multicenter, non-randomized, single-arm, open-label clinical study of the
Safety & Performance
of the TIVUS™ System
Jonas M., LINC 2013

10. TIVUS™ I Study
Jonas M., LINC 2013

11. TIVUS™ I Study-Case Study
Jonas M., LINC 2013 11
| Confidential

12. TIVUS™ I Study-Baseline
*Dipper 21%
Jonas M., LINC 2013

13. TIVUS™ I Study-Baseline
Selective Renal Angiography- Baseline R L
6Fr TIVUS™ Catheter, 0.014” OTW, 6Fr Steerable Introducer
30 seconds per treatment point
Jonas M., LINC 2013

14. No Spasm, Normal Renal Arteries No AE, SAE or Complications
TIVUS™ I Study-Procedure
End of Procedure:
No Spasm, Normal Renal Arteries
No AE, SAE or Complications R L
Jonas M., LINC 2013

15. TIVUS™ I Study-Post Procedure
Jonas M., LINC 2013

16. TIVUS™ I Study-Preliminary Results
No safety concerns
No device malfunction or complication
No SAE
Successfully & effectively delivered ultrasonic treatment
Minimal Patient discomfort compared with RF technology
Short Duration per treatment point
Protection of the luminal artery wall
Jonas M., LINC 2013

17. Cardiosonic TIVUSTM Technology Special Capabilities for Renal Denervation
Renal denervation from the aorta (around the ostium)
Denervation of renal arteries with early bifurcation
Renal denervation through a renal stent
Venous access renal artery denervation - possibly for problematic arterial anatomies
Probable: renal denervation through soft plaque/stenosis

18. Renal artery denervation from the aorta (around the ostium)XN A
Renal Nerve
Thermal Effect Region B XN
High Intensity Ultrasound Energy B A
Histopathology (H&E)
XN: Necrosed Nerves
Solid Black line:
Thermal damage border
TIVUSTM Catheter

19. Renal Denervation of Renal Artery with Early Bifurcation
Cardiosonic TIVUSTM treatment head (ultrasonic transducer)
10mm

20. Denervation Through a Renal Stent
Histopathology: Endoneural degenerated cells some with vacuolated cytoplasm (black border region) with adjacent cells with pyknotic nuclei. H&E. (CVPath Institute)
Stent #2

21. Venus Access Renal Artery Denervation: TIVUSTM in Vena-Cava Positioning
Histopathology (H&E)
XN: Necrosed Nerves
Solid Black line:
Thermal damage border
Dashed Green Line: Vena cava
General: intact endothelium of the vena-cava and renal artery (no thermal damage or other)

22. Treatment Through a Human Atherosclerotic Plaque (amputation, ex-vivo)
Histopathology (H&E)
Solid Black line:
Thermal damage border
General: intact endothelium of the artery and plaque (no thermal damage or other)

23. Thank you !